Research ArticleInfectious Disease

Two-mAb cocktail protects macaques against the Makona variant of Ebola virus

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Science Translational Medicine  09 Mar 2016:
Vol. 8, Issue 329, pp. 329ra33
DOI: 10.1126/scitranslmed.aad9875
  • Fig. 1. Characterization of MIL77.

    (A) HILIC analysis of the peptide N-glycosidase (PNGase) F enzymatically released N-glycans with 2-AB fluorescence tag. MAb1, a recombinant humanized immunoglobulin G1 (IgG1) mAb produced with normal CHOK1 cells that has typical N-glycan profile, is used as control. GlcNac, N-acetylglucosamine. (B) Affinity of MIL77 components for human CD16 (FcγRIIIa), determined by enzyme-linked immunosorbent assay (ELISA). OD450, optical density at 450 nm. (C) Time-concentration curves for six animals given MIL77 (150 mg/kg) (1 + 2 + 3).

  • Fig. 2. Protection of guinea pigs by MIL77.

    (A) Survival curves showing the survival of various groups of guinea pigs infected with EBOV/GA on day 0 and treated on day 3 with the specified treatment (5 mg per animal unless specified). (B) Weight change of guinea pigs from (A) over the first 16 days of the experiment. Groups: ZMapp: c13C6 + c2G4 + c4G7; ratio, 1:1:1; total dose, 5 mg per animal. Plant2: c13C6 + c2G4; ratio, 1:2, total dose, 5 mg per animal. MIL2.5: 2.5 mg of MIL77 (1 + 2 + 3). MIL5: 5 mg of MIL77 (1 + 2 + 3). PBS: 1 ml of PBS.

  • Fig. 3. Protection of NHPs by MIL77.

    (A) Timeline of the experiment. Arrows: red, challenge day; blue, treatment + exam; black, exam. PFU, plaque-forming units. (B) Survival. (C) Viremia measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). (D) Clinical score. (E) Rectal temperature.

  • Fig. 4. Clinical parameters of NHPs challenged with EBOV/Mak and treated with PBS or MIL77.

    (A) Liver function, illustrated by alkaline phosphatase (ALP) and alanine aminotransferase (ALT). (B) Kidney function, illustrated by total bilirubin (TBIL) and blood urea nitrogen (BUN). CRE, creatinine. (C) Blood count, illustrated by lymphocyte count (LYM), neutrophil count (NEU), and platelet count (PLT).

  • Fig. 5. Protection of NHPs by ZMapp (c13C6 + c2G4).

    (A) Timeline of the experiment. Arrows: red, challenge day; green, treatment + exam; black, exam. (B) Survival. (C) Viremia measured by qRT-PCR. (D) Clinical score. (E) Rectal temperature.

  • Fig. 6. Clinical parameters of NHPs challenged with EBOV/Mak and treated with PBS or ZMapp (c13C6 + c2G4).

    (A) Liver function, illustrated by ALP and ALT. (B) Kidney function, illustrated by BUN and CRE. (C) Blood count, illustrated by LYM, NEU, and PLT.

Supplementary Materials

  • www.sciencetranslationalmedicine.org/cgi/content/full/8/329/329ra33/DC1

    Fig. S1. Affinity ELISA comparing the binding affinity of the ZMapp antibodies and their MIL77 counterparts.

    Fig. S2. Comparing the neutralization potential of the ZMapp antibodies and their MIL77 counterparts.

    Fig. S3. The competition ELISA assessing the binding specificities among MIL77-1, MIL77-2, and MIL77-3 antibodies.

    Table S1. Characterization of the enzymatically released and 2-AB–labeled N-glycans from the three MIL77 mAbs by LC-MS.

  • Supplementary Material for:

    Two-mAb cocktail protects macaques against the Makona variant of Ebola virus

    Xiangguo Qiu,* Jonathan Audet, Ming Lv, Shihua He, Gary Wong, Haiyan Wei, Longlong Luo, Lisa Fernando, Andrea Kroeker, Hugues Fausther Bovendo, Alexander Bello, Feng Li, Pei Ye, Michael Jacobs, Giuseppe Ippolito, Erica Ollmann Saphire, Shengli Bi, Beifen Shen, George F. Gao, Larry Zeitlin, Jiannan Feng,* Boyan Zhang,* Gary P. Kobinger*

    *Corresponding author. E-mail: xiangguo.qiu{at}phac-aspc.gc.ca (X.Q.); gary.kobinger{at} phac-aspc.gc.ca (G.P.K.); fengjiannan77{at}qq.com (J.F.); zhangby{at}mab-works.com (B.Z.)

    Published 9 March 2016, Sci. Transl. Med. 8, 329ra33 (2016)
    DOI: 10.1126/scitranslmed.aad9875

    This PDF file includes:

    • Fig. S1. Affinity ELISA comparing the binding affinity of the ZMapp antibodies and their MIL77 counterparts.
    • Fig. S2. Comparing the neutralization potential of the ZMapp antibodies and their MIL77 counterparts.
    • Fig. S3. The competition ELISA assessing the binding specificities among MIL77-1, MIL77-2, and MIL77-3 antibodies.
    • Table S1. Characterization of the enzymatically released and 2-AB–labeled N-glycans from the three MIL77 mAbs by LC-MS.

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